ISR Awards

Creating a National Resource for Genetic Research: SUPPLEMENT

Genotyping technology is advancing at a rapid pace, and we hope that the resource we are constructing will have some durable value, which means we should seek to use the best available technology within reach of the financial resources available. The RC2 proposed using an Illumina 1million SNP platform (Illumina is the preferred chip manufacturer for DNA samples based on saliva, as ours are). Since that time Illumina has released two new chips?the Omni-1 quad which has about the same number of SNP calls as the chip in the original proposal but with locations optimized based on previous GWAS findings, and now the 2.5M beadchip. The 150% increase in number of SNPs translates to coverage of SNPs with a 2% population frequency of allele variation, compared with 5% for the Omni-1 chip. As genetics moves away from (unsuccessful) models of common single gene variants with large effects on phenotypic traits and toward models of rare variants and gene-gene interactions, the coverage of rarer variations becomes increasingly important.

A key strength of the HRS sample for genetic analysis is its substantial representation of African-Americans. This population benefits greatly from the technology behind the new 2.5m chip. Earlier generations of chips were designed based on the HapMap sample, which had weaker than expected representation of the actual variation in genomes of populations of recent African origin. The 1000 Genome Project that forms the basis for the new generation chips captures much more of the genomic variation seen in individuals with significant recent African ancestry, and has led to the inclusion of many thousands of additional SNPs that better represent the spectrum of genetic variation among African-Americans. My understanding is that there may be ARRA funds available dedicated to the study of minority health, and we feel that using the improved chip technology on samples from African Americans in the HRS would be a fitting use for some of this money.